In megakaryocytes, the maturation process and oxidative stress response appear to be closely related. It has been suggested that increased oxygen tension and reactive oxygen species (ROS) promote megakaryopoiesis and that the expression of stress-responsive genes responsible for ROS elimination declines during megakaryocytic maturation. NF-E2 p45 is an essential regulator of megakaryopoiesis, while Nrf2 is a key activator of stress-responsive genes. Since p45 and Nrf2 have similar DNA binding specificities, we hypothesized that p45 competes with Nrf2 to repress stress-responsive genes and achieves favorable intracellular conditions to allow ROS to be efficiently utilized as signaling molecules. We conducted comprehensive gene expression profiling with wild-type and p45-null megakaryocytes and examined the functional relationship between p45 and Nrf2. We found that two characteristic gene clusters are defined within p45 target genes; platelet genes and cytoprotective genes. The former are unique targets activated by p45, whereas the latter are common targets of p45 and Nrf2. Further analysis suggested that, as a less efficacious activator, p45 maintains moderate expression of cytoprotective genes through competing with Nrf2 and promotes ROS accumulation. Increased ROS enhanced platelet gene expression. These results suggest that p45 dominates over Nrf2 to enhance megakaryocytic maturation by promoting ROS accumulation.

Solute removal performances of dialyzers are dependent not only on the solute permeabilities of the membrane but also on the module design. We have investigated how the packing density of hollow fiber (PDF) affects the solute removal performances. A series of 4 polyester polymer alloy membrane test dialyzers were assembled with varying PDFs of 29.6%, 35.3%, 44.1%, and 53.1%. Clearances (C(L)) were measured in vitro for creatinine (MW113), vitamin B(12)(MW1355), and chymotrypsin (MW25300) with various Q(B)=100 to 400 and Q(D)=350 to 650 mL/min in the absence of net ultrafiltration. When Q(B) was <or=300 mL/min, no significant changes were found in creatinine C(L) with the increase of PDF up to 35.3%. A slightly greater increase was found in C(L) when Q(B)=400 mL/min. Clearances for vitamin B(12), however, increased with the increase of PDF in the range of 29.6% to 35.3%. The effects of PDF on C(L) were greater with larger Q(B). More importantly, an abrupt increase of C(L) was found when PDF was increased from 44.1% to 53.1%. According to a rigorous mathematical model, this may be caused by the internal filtration, which is reverse ultrafiltration occurring in a dialyzer at any given time. No significant increase was found in chymotrypsin C(L) when the PDF was <or=35.3%, which suggested that C(L) for large molecules was strongly dependent on the solute permeability rather than the conditions of flow patterns. A very steep increase was also found in C(L) for chymotrypsin when the PDF was >44.1%, which was also considered to be due to the internal filtration. Packing density of hollow fiber can be optimized in terms of solute removal performances when the target solute and therapeutic conditions are specified.

During 1997, two new viruses were isolated from outbreaks of disease that occurred in horses, donkeys, cattle and sheep in Peru. Genome characterization showed that the virus isolated from horses (with neurological disorders, 78% fatality) belongs to a new species the Peruvian horse sickness virus (PHSV), within the genus Orbivirus, family Reoviridae. This represents the first isolation of PHSV, which was subsequently also isolated during 1999, from diseased horses in the Northern Territory of Australia (Elsey virus, ELSV). Serological and molecular studies showed that PHSV and ELSV are very similar in the serotype-determining protein (99%, same serotype). The second virus (Rioja virus, RIOV) was associated with neurological signs in donkeys, cattle, sheep and dogs and was shown to be a member of the species Yunnan orbivirus (YUOV). RIOV and YUOV are also almost identical (97% amino acid identity) in the serotype-determining protein. YUOV was originally isolated from mosquitoes in China.

The present patient developed a severe rectal ulcer more than 1 month after having received external beam radiation therapy for prostate cancer. Surveillance endoscopy every 3 months demonstrated healing of this rectal ulcer using a novel therapy. He was given enemas with ecabet sodium, which provides physical protection and promotes healing by increasing prostaglandin E(2), and this process induced squamous metaplasia that halted the progression of the ulcer of radiation proctitis as a late-phase reaction. Intrapapillary capillary loops were visualized with magnified narrow band imaging at the healing ulcer site as seen via the esophagus and, moreover, demonstrated histologically.

A Gram-positive, endospore-forming lactic acid bacterium was isolated from spoiled orange juice. The organism, strain QC81-06(T), grew microanaerobically or anaerobically at 30-45 degrees C (optimum 35 degrees C) and pH 3.5-5.5 (optimum pH 4.5), and produced acid from various sugars. D-lactic acid was produced. It contained menaquinone-7 as the major isoprenoid quinone. The G+C content of the genomic DNA was 47.5 mol%. The predominant cellular fatty acids of the strain were iso-C16:0, anteiso-C15:0 and anteiso-C17:0. Phylogenetic analyses based on the 16S rRNA gene (16S rDNA) and gyrB gene (DNA gyrase B subunit gene) revealed that strain QC81-06(T) clustered with Sporolactobacillus species but the strain was clearly distinct from other Sporolactobacillus species with significant bootstrap values. The level of the 16S rDNA sequence similarities between strain QC81-06(T) and the other strains of the cluster was 96.1-97.1% and the level of gyrB gene sequence similarities between strain QC81-06(T) and the other strains was 75.1-77.2%. On the basis of these results, strain QC81-06(T) should be classified as a novel Sporolactobacillus species. The name Sporolactobacillus putidus is proposed for this organism. The type strain of Sporolactobacillus putidus is strain QC81-06(T)(=DSM 21265(T)=JCM 15325(T)).

PURPOSE: The aim of this study was to pathologically investigate the developmental pattern of undifferentiated mucosal gastric cancer and to determine safe surgical margins for curative resection by endoscopic resection. RESULTS: Intramucosal cancer spread, or the width of the proliferative zone, was pathologically investigated in 47 cases of undifferentiated mucosal gastric cancer of size 20 mm or smaller without ulceration (scars). The 47 cases comprised 40 IIc and 7 IIb cases. The IIc cases consisted of 5 (12.5%) of intermediate-layer type (cancer localized at the intermediate layer of the mucosa), 31 (77.5%) of superficial type, and 4 of whole-layer type (10%). The IIb cases consisted of six of intermediate-layer type (85.7%) and one of superficial type (14.3%). The width of the proliferative zone in the 40 IIc cases ranged from 0 to 2,390 mum (average 605.5 mum). There was no significant correlation between width of proliferative zone and background mucosa. With regard to lesion size, average width was 243.6 mum in cases with longest diameter </=5 mm, while it was significantly larger (617.1 mum) in cases with diameter >5 mm. CONCLUSIONS: In endoscopic treatment of undifferentiated mucosal gastric cancer of size 20 mm or smaller without ulceration (scars), the lateral safety margin should be 3 mm or more.

BACKGROUND/AIMS: Iodine staining of the esophagus has been shown to be useful in detecting esophageal cancer. Narrow band imaging (NBI), a new endoscopic lighting system, visualizes the microvasculature of the gastrointestinal (GI) mucosa. To evaluate the detectability of early esophageal cancer by screening endoscopy assisted with NBI as compared with that assisted with iodine staining. METHODOLOGY: Design: A prospective comparative study. Setting A single endoscopy unit. Patients: Forty-nine consecutive patients, consisting of 40 males and 9 females with a mean age of 67, most of whom were at high risks for esophageal cancer (heavy drinker and smoker, history of cancer especially of head and neck, etc.). Intervention: Following conventional endoscopic observation, the esophagus was observed with NBI for possible cancerous lesions. Dark-brown areas on NBI were defined as NBI-positive areas. Esophageal mucosa was subsequently stained with 1.5% iodine, and both findings were compared. Finally, the areas discolored by iodine stain were biopsied for histological evaluation. Main outcome measurements: The sensitivity, specificity, and positive predictive value (PPV) of endoscopic detection of esophageal cancer. RESULTS: Squamous cell carcinoma was detected in 5 out of 118 areas. Esophageal cancers detected were all both NBI-positive and discolored by iodine staining. Sensitivity, specificity, and PPV of NBI-positive areas for cancer were 100%, 59%, and 9.8%, respectively. On the other hand, the discolored areas with iodine staining for cancer were 100%, 4.4%, and 4.4%, respectively. NBI observation was significantly superior to iodine staining for detecting esophageal cancer (p < 0.02). Limitation: In this study, the endoscopist engaged was not blinded and the assessment was not standardized. CONCLUSIONS: Esophageal endoscopy assisted with NBI was more useful for detecting early esophageal cancer than that assisted with iodine staining.

The novel gold nanoparticle, which was stabilized with pi-conjugated molecules bearing functional groups at the terminals, was prepared via conventional procedure by using 5-bromo-2,2'-bithiophene-5'-thiol as a stabilizer. The gold nanoparticle (ca. 3 nm-diameter) showed good dispersion stability in various organic solvents, and its electrochemical and spectroscopic study revealed peculiar properties originated in the pi-conjugated molecular stabilizer, bithiophene derivative. The Pd-catalyzed coupling reaction on the gold nanoparticle was first achieved by using the gold nanoparticle bearing bromo groups at the particle surface and the model boronic acid molecule, 5-formyl-2-thiopheneboronic acid, to yield the terthiophene derivatives on the gold nanoparticle. The 1H-NMR, UV, and TGA analysis supported the progress of the coupling reaction on the gold nanoparticle. This Pd-catalyzed coupling reaction was applied with the borate-terminated polythiophene to form polythiophene/gold nanoparticle alternate network film. The electron microscopic images supported the formation of the network structure. The high electric conductivity on the network film suggested that the conductive characteristic of the film originated from that of the pi-conjugated polythiophene backbone connected with the gold nanoparticle.

OBJECTIVE: To explain the accumulation of (18)F-2-deoxy-2-fluoro-glucose ((18)FDG) on positron emission tomography (PET) in the stomach and differences in its pattern, we focus on the accumulation pattern in association with endoscopic findings of the gastric mucosa and Helicobacter pylori (Hp) infection. METHODS: Of 599 cases undergoing (18)FDG-PET examinations, we retrospectively analyzed the pattern of (18)FDG accumulation in the stomach, findings of upper gastrointestinal endoscopy, and Hp infection. The pattern of (18)FDG accumulation was classified into three groups: localized accumulation only in the fornix (Group A, 32 patients), diffuse accumulation throughout the entire stomach (Group B, 49 patients), and no accumulation (Group C, 191 patients). RESULTS: Regarding the relation between Hp infection and (18)FDG accumulation, Hp infection was positive in 56.3% of Group A, 73.5% of Group B, and 24.1% of Group C, with significant differences (p < 0.001). Regarding the relation between (18)FDG accumulation and gastric mucosal inflammation, when Groups A and B were compared with Group C, nearly half of the cases in the former groups had papular redness with a significantly higher frequency of redness and erosion. Three cases found to have malignant tumor were limited to the former groups. One MALT lymphoma case was also found in the same group. Accumulation of (18)FDG largely corresponded to mucosal inflammation including superficial gastritis and erosive gastritis, and therefore the main cause of non-specific (18)FDG accumulation was considered to be inflammatory mucosa (mainly redness). The accumulation pattern was not associated with atrophic changes of the gastric mucosa or with Hp infection, but with mucosal inflammatory changes, including redness and erosion localized to the fornix. CONCLUSIONS: Accumulation of (18)FDG in the stomach suggests a high probability of the presence of inflammatory change in the gastric mucosa forming a background for the development of cancer or malignant lymphoma, and thus requires further endoscopic examinations.

There have been various attempts to redirect the cell entry receptor tropism of the murine leukemia virus vectors. We have recently reported the successful retargeting of the ecotropic Moloney murine leukemia virus vector. This vector (S3-D84K) contains a viral envelope (Env) protein into which a full-length (68 aa) stromal cell-derived factor-1alpha (SDF-1alpha) was inserted at Pro-79. The S3-D84K vector transduces a certain human cell line through the CXC chemokine receptor 4 (CXCR4) at a titre of about 10(4) c.f.u. ml(-1). Here, the S3-D84K vector was found to transduce another human cell line through CXCR4 with a titre close to 10(6) c.f.u. ml(-1). The SDF-1alpha ligand of the S3-D84K Env protein was modified in different ways. In one, C-terminal truncations (by 3-51 aa) with or without a Cys-to-Gly change were performed, and in the other, Cys-to-Ala changes of the disulfide-forming cysteines without truncation were made. Seven truncation and three alanine mutant chimeric Env proteins were examined for virion incorporation, and the retroviral vectors displaying the mutant protein were examined for CXCR4 binding and retargeted transduction. Two mutant vectors showed transduction through CXCR4 with titres not higher than those of the S3-D84K vector, while the other mutant vectors minimally transduced cells through CXCR4 either due to a defect in virion incorporation of the chimeric Env protein or an inability to bind to CXCR4. These results suggest that a full-length sequence that may fold into a distinct domain within the chimeric Env protein is preferable as a targeting ligand.